Heparin-binding protein (HBP), also known as azurocidin, has multiple functions in the inflammatory process, especially during severe infections. Beside its antimicrobial properties, HBP may induce vascular leakage leading to extravascular efflux, which is an important pathophysiologic event in the development of septic shock. Not surprisingly, high HBP plasma levels are found in severe sepsis patients and in septic shock patients as well as in serious infections associated with endothelial damage. In the present issue of Critical Care, Linder and colleagues demonstrate new aspects of HBP daily monitoring in ICU patients. The authors observed that high HBP plasma levels are associated with an increased mortality rate in both septic and nonseptic critically ill patients, indicating that HBP may be a reliable prognostic biomarker. However, there are some limitations hindering rapid translation of these interesting findings into the daily routine. First, the group of nonseptic critically ill patients (n = 28) enrolled in the study was rather small as compared with the septic group (n = 151). Moreover, 50% of nonseptic patients developed infection while hospitalized in the ICU, and to classify them as truly nonseptic patients is problematic. Second, there is a lack of a routine diagnostic method for HBP analysis. Nevertheless, if the results of the present study are validated in large clinical trials in different ICU populations and cost-effectiveness data become available, the serial HBP measurements will have a promising future.